Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice
Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene en...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/965056 |
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| _version_ | 1850169728743505920 |
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| author | Manal Alkan François Machavoine Rachel Rignault Julie Dam Michel Dy Nathalie Thieblemont |
| author_facet | Manal Alkan François Machavoine Rachel Rignault Julie Dam Michel Dy Nathalie Thieblemont |
| author_sort | Manal Alkan |
| collection | DOAJ |
| description | Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC−/− mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC−/− mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC−/− mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response. |
| format | Article |
| id | doaj-art-a9e5ec5bd9b143638d8229a926e4eec9 |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-a9e5ec5bd9b143638d8229a926e4eec92025-08-20T02:20:40ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/965056965056Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD MiceManal Alkan0François Machavoine1Rachel Rignault2Julie Dam3Michel Dy4Nathalie Thieblemont5Université Paris Descartes, 75014 Paris, FranceUniversité Paris Descartes, 75014 Paris, FranceUniversité Paris Descartes, 75014 Paris, FranceUniversité Paris Descartes, 75014 Paris, FranceUniversité Paris Descartes, 75014 Paris, FranceUniversité Paris Descartes, 75014 Paris, FranceRecent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC−/− mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC−/− mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC−/− mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response.http://dx.doi.org/10.1155/2015/965056 |
| spellingShingle | Manal Alkan François Machavoine Rachel Rignault Julie Dam Michel Dy Nathalie Thieblemont Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice Journal of Diabetes Research |
| title | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
| title_full | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
| title_fullStr | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
| title_full_unstemmed | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
| title_short | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
| title_sort | histidine decarboxylase deficiency prevents autoimmune diabetes in nod mice |
| url | http://dx.doi.org/10.1155/2015/965056 |
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